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How does ZFP36 reshape metabolism after growth signals?

Growth factors induce ZFP36, which binds and decays metabolic enzyme/transporter mRNAs—especially Eno2—tuning glycolytic metabolism.

Source

ZFP36-mediated mRNA decay regulates metabolism

Cicchetto AC, Jacobson EC, Sunshine H, et al. · Cell reports · 2023

doi.org/10.1016/j.celrep.2023.112411Read the full paper ↗45 citationscc by

What they did

Mapped ZFP36 induction and eCLIP targets after growth-factor stimulation in MEFs, validated Eno2 decay, metabolomics, and retinal angiogenesis after endothelial Zfp36 loss.

What they found

ZFP36 family members are acute growth-factor immediate-early genes; they bind many metabolic mRNAs and promote Eno2 mRNA decay; loss elevates ENO2/PEP and alters the metabolome; regulation appears in neonatal retinal angiogenesis.

The limits

What it doesn't show

Does not prove Eno2 is the sole metabolic effector of ZFP36 in every tissue or that ZFP36 drugs would safely remodel metabolism clinically.

Key terms

ZFP36
RNA-binding protein family that promotes ARE-mediated mRNA decay.
ARE
AU-rich element in 3′ UTRs that recruits decay factors.
ENO2
Enolase 2, a glycolytic enzyme producing phosphoenolpyruvate.
eCLIP-seq
Crosslinking method to map RNA-binding protein targets.
Immediate-early gene
Gene induced rapidly by stimuli without needing new protein synthesis cofactors for onset.

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Quiz yourself

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ZFP36 is induced here by:

Common questions

What induces ZFP36 here?

Acute growth-factor / serum signaling.

Key metabolic target validated?

Enolase 2 (Eno2) mRNA decay.

What happens without ZFP36 family?

Metabolic mRNAs/metabolites shift; ENO2 and PEP rise.

In vivo context?

Endothelial ZFP36 regulates ENO2 during retinal angiogenesis.

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